Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on scratching behavior in mice

Ono, Rie; Kagawa, Yoto; Takahashi, Yuji; Akagi, M; Kamei, Chiaki

doi:10.1016/j.intimp.2009.11.015

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…The neuro-protective/ trophic properties of NGF are well established [24, 30, 31], albeit therapeutic applications are currently limited due to pathogenic side effects including neuropathic [4, 5] and deep tissue pain [10, 11] atopic dermatitis [7 – 9], arthritis, asthma [10, 12, 13], intervertebral disc degeneration [14] and cancer. [15 – 17] Therefore, there is a need for identification of small MW neurotrophic compounds that may have therapeutic value in treatment of peripheral/CNS injury or neurodegenerative disorders, without the limitations of endogenous neurotrophins.…”

Section: Discussionmentioning

confidence: 99%

“…While most drug regimens have capacity to improve quality of life, they do not address the underlying etiology of the disease and thereby do not arrest progression degenerative processes. Although endogenous synthesis of trophic molecules such as nerve growth factor (NGF) [1], brain-derived neurotrophic factor (BDNF) and neurotrophin-3/neurotrophin-4 can effectively stimulate neuronal growth/repair [2, 3], therapeutic applications are limited by a wide range of negative side effects such as neuropathic pain [4, 5], bladder/urinary pain [6], itchy skin (pruritus) atopic dermatitis [7 – 9], deep tissue tenderness [10, 11], exacerbated inflammatory conditions such as arthritis, asthma [10, 12, 13], inter-vertebral disc degeneration [14] and cancer [15 – 17]. Furthermore, elevated levels of NGF in various neuronal tissue can lead to behavioral/cognitive disorders such as autism [18], bipolar [19] and attention deficit/hyperactivity disorder.…”

Section: Introductionmentioning

confidence: 99%

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Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells

et al. 2015

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Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use of human neurotrophic agents such as nerve growth factor (NGF) are limited due to hampered transport across the blood brain barrier (BBB) and a large number of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is a continued need for discovery of small molecule NGF mimetics that can penetrate the BBB and initiate CNS neuronal outgrowth/regeneration. In the current study, we conduct an exploratory high-through-put (HTP) screening of 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio with only 1/1144 tested substances (<111.25 µg/mL) being capable of inducing neurite outgrowth in a dose dependent manner, identified as; Mu Bie Zi, Momordica cochinchinensis seed extract (MCS). To quantify the neurotrophic effects of MCS, 36 images (n = 6) (average of 340 cells per image), were numerically assessed for neurite length, neurite count/cell and min/max neurite length in microns (µm) using Image J software. The data show neurite elongation from 0.07 ± 0.02 µm (controls) to 5.5 ± 0.62 µm (NGF 0.5 μg/mL) and 3.39 ± 0.45 µm (138 μg/mL) in MCS, where the average maximum length per group extended from 3.58 ± 0.42 µm (controls) to 41.93 ± 3.14 µm (NGF) and 40.20 ± 2.72 µm (MCS). Imaging analysis using immunocytochemistry (ICC) confirmed that NGF and MCS had similar influence on 3-D orientation/expression of 160/200 kD neurofilament, tubulin and F-actin. These latent changes were associated with early rise in phosphorylated extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187) at 60 min with mild changes in pAKT peaking at 5 min, and no indication of pMEK involvement. These findings demonstrate a remarkable infrequency of natural products or polyphenolic constituents to exert neurotrophic effects at low concentrations, and elucidate a unique property of MCS extract to do so. Future research will be required to delineate in depth mechanism of action of MCS, constituents responsible and potential for therapeutic application in CNS degenerative disease or injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells

et al. 2015

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POPs and Skin

Leijs

Koppe

Kraus

et al. 2017

Environment and Skin

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Serum from Methimazole-Treated Patients Induces Activation of Aryl Hydrocarbon Receptor, a Transcription Factor That Binds to Dioxin-Response Elements

Ishikawa

Okinaga

Takahashi

et al. 2012

Thyroid

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Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.

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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on scratching behavior in mice

Cited by 3 publications

References 28 publications

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells

POPs and Skin

Serum from Methimazole-Treated Patients Induces Activation of Aryl Hydrocarbon Receptor, a Transcription Factor That Binds to Dioxin-Response Elements

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